Animal models are used for the evaluation of acellular pertussis vaccine components before use in clinical trials and administration to humans. The aerosol challenge model provides a reproducible system for the study of virulence factors and immunity involved in respiratory infection and subsequent disease. We are evaluating purified antigens of B. pertussis for their ability to protect neo-natal mice against lethal respiratory infection. Active immunization with glutaraldehyde-inactivated pertussis toxin, the B oligomer of pertussis toxin, filamentous hemagglutinin and the 69kDa outer membrane protein of B. pertussis elicits specific antibody in the serum and lungs of mice and protects neonatal mice against lethal respiratory infection. Monoclonal antibodies directed against pertussis toxin and the 69kDa outer membrane protein also protect when passively administered. Current studies are in progress to evaluate additional soluble and membrane-associated proteins, as well as a genetically engineered non-toxic mutant of pertussis toxin for their protective ability and antigenicity.